Study on the Effect of Oral Diammonium Glycyrrhizinate in Attenuating Toxicity and Enhancing Efficacy of CAR-T Cell Therapy

Официальное название

A Single-Center, Prospective, Randomized Controlled Clinical Study of Oral Diammonium Glycyrrhizinate for Attenuating Toxicity and Enhancing Efficacy of CAR-T Cell Therapy

Обзор

The purpose of this study is to evaluate the effect of oral diammonium glycyrrhizinate in reducing toxicity and enhancing efficacy of CAR-T cell therapy in patients with large B-cell lymphoma. Two main questions are addressed: 1) Can oral diammonium glycyrrhizinate reduce the incidence and severity of CRS induced by CAR-T cells? 2) Can oral diammonium glycyrrhizinate synergistically increase the therapeutic efficacy of CAR-T cell therapy?

Подробное описание

Current studies suggest that regulating pyroptosis may play a role in reducing toxicity and enhancing efficacy during CAR-T cell therapy by alleviating cytokine release syndrome (CRS) and improving the tumor microenvironment (TME). Glycyrrhizic acid has been clearly shown to inhibit pyroptosis and is widely recognized for its broad-spectrum anti-inflammatory effects and ability to improve the TME. Therefore, it holds promise as an ideal intervention for preventing/treating CRS induced by CAR-T cells and for synergistically enhancing the therapeutic efficacy of CAR-T cell therapy. Accordingly, this study aims to investigate the effect of oral diammonium glycyrrhizinate in reducing toxicity and enhancing efficacy of CAR-T cell therapy in patients with large B-cell lymphoma.

Вмешательства

• Препарат Diammonium glycyrrhizinate Capsules
  For the experimental group, at the time of CAR-T cell infusion, oral diammonium glycyrrhizinate is given in addition to standard clinical care (first two weeks: 150 mg three times daily; thereafter, 100 mg once daily, continued orally for 2 years).

Первичные конечные точки

• CRS [Срок оценки: Within 28 days post CAR-T cell infusion]

Вторичные конечные точки (7)

• Complete remission rate [Срок оценки: Assessments are performed every 3 months within the first two years after CAR-T infusion]
• Objective Response Rate [Срок оценки: Assessments are performed every 3 months within the first two years after CAR-T infusion]
• Duration of response [Срок оценки: Assessments are performed during the first two years following CAR-T infusion.]
• Overall survival [Срок оценки: Up to 2 years as per long-term follow-up mentions]
• Progression-free survival [Срок оценки: Assessments are performed during the first two years following CAR-T infusion]
• Level of CAR-T cell persistence [Срок оценки: Assessments are performed every 3 months within the first year after CAR-T infusion]
• Adverse events [Срок оценки: Assessments are performed during the first two years following CAR-T infusion]

Критерии участия

Критерии включения

• Age ≥ 18 years.
• Patients diagnosed with large B-cell lymphoma and receiving CAR-T cell therapy.
• Adequate organ function prior to enrollment: ALT and AST ≤ 2.5 × ULN (upper limit of normal); may be extended to ≤5 × ULN in patients with liver involvement; serum total bilirubin < 34 μmol/L; creatinine clearance > 30 mL/min; cardiac ejection fraction (EF) ≥ 40%, with no pericardial effusion or significant arrhythmia; room air SpO₂ ≥ 92%.
• No central nervous system involvement of lymphoma confirmed by MRI prior to enrollment.
• Subjects of childbearing potential must agree to use highly effective contraceptive methods.
• The subject or their legal guardian must be able to understand and voluntarily sign a written informed consent form.

Критерии исключения

• Presence of a prior malignancy (other than the disease under study) that requires ongoing systemic treatment for any other malignant tumor.
• Presence of any life-threatening disease, medical condition, or organ system dysfunction that, in the investigator's judgment, may compromise patient safety or interfere with the interpretation of safety or efficacy data.
• Current or prior central nervous system (CNS) involvement by malignancy.
• Receipt of allogeneic stem cell transplantation within 6 months prior to enrollment, or autologous stem cell transplantation within 3 months prior to enrollment; and the patient must have no signs or symptoms of graft-versus-host disease and must not be receiving immunosuppressive therapy.
• Intolerance or allergy to glycyrrhizic acid preparations.
• Patient refuses to comply with the study requirements to complete the research work.
• In the investigator's judgment, the patient is unable to complete the study or comply with the study requirements (due to administrative reasons or other reasons), or is considered unsuitable for clinical trial participation for other reasons.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Поддерживающая терапия

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07616271 · TJ-IRB202603111

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗